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Biomedical subjects

E Rose

Publications and source records attributed to E Rose.

At least 37 records · Page 2Linked to original sources
PubMed1999

Intravenous immunoglobulin reduces anti-HLA alloreactivity and shortens waiting time to cardiac transplantation in highly sensitized left ventricular assist device recipients.

BACKGROUND: Recipients of left ventricular assist devices (LVADs) develop prominent B-cell hyperreactivity. We investigated the influence of anti-HLA antibodies on waiting time to cardiac transplantation in LVAD recipients and compared the effects of 2 immunomodulatory regimens on anti-HLA serum reactivity. METHODS AND RESULTS: Fifty-five previously nonsensitized LVAD recipients of a TCI device implanted between 1990 and 1996 were studied. Patients with anti-HLA antibodies received monthly courses of either intravenous immunoglobulin (IVIg) or plasmapheresis, in conjunction with cyclophosphamide. The effects of these regimens on anti-HLA alloreactivity and waiting time to transplantation were then determined by Kaplan-Meier log-rank statistics, nonparametric Wilcoxon rank-sum test, and Student's t test. Prolongation in transplant waiting time was related to serum IgG anti-HLA class I alloreactivity. Infusion of IVIg (2 g/kg) caused a mean reduction of 33% in anti-HLA class I alloreactivity within 1 week. Waiting time to transplantation was significantly reduced by IVIg therapy and subsequently approximated that in nonsensitized patients. Side effects of IVIg (2 g/kg) were minimal and related primarily to immune complex disease. Although plasmapheresis caused a similar reduction in alloreactivity to IVIg, this effect was achieved after longer treatment. Moreover, plasmapheresis was associated with an unacceptably high frequency of infectious complications. In patients resistant to low-dose (2 g/kg) IVIg therapy, high-dose (3 g/kg) IVIg was effective in reducing alloreactivity but was associated with a high incidence of reversible renal insufficiency. CONCLUSIONS: These results indicate that IVIg is an effective and safe modality for sensitized recipients awaiting cardiac transplantation, reducing serum anti-HLA alloreactivity and shortening the duration to transplantation. The therapeutic and safety profile of IVIg would appear to be superior to plasmapheresis.

Graft Rejection↗
PubMed1998

Low incidence of myocardial recovery after left ventricular assist device implantation in patients with chronic heart failure.

BACKGROUND: Mechanical, histological, and biochemical improvement has been described in patients after left ventricular assist device (LVAD) support. Explantation of the LVADs without heart transplantation has been described in selected patients who received this therapy as a bridge to transplantation. METHODS AND RESULTS: A retrospective review of patients receiving a mechanical bridge to transplantation at Columbia Presbyterian Hospital after July 21, 1991, was performed to determine the incidence of patients in whom the device was successfully explanted. From August 1, 1996, to February 1, 1998, we prospectively attempted to identify potential explant candidates by the use of exercise testing. During this time, we recruited 39 consecutive patients after insertion of the Thermo Cardiosystems vented electric device to participate in the following study. Approximately 3 months after device implantation, a maximal exercise test with hemodynamic monitoring and respiratory gas analysis was performed with the LVAD in the automated mode. The electric device was interfaced with a pneumatic console such that the rate could be decreased to 20 cycles/min. Hemodynamic measurements were recorded as the device rate was decreased. A repeat exercise test was then performed if the patient remained hemodynamically stable. A retrospective chart review of 111 LVAD recipients at our institution identified only 5 successful explant patients. Eighteen of the 39 patients were studied. Fifteen patients exercised with maximal device support. At peak exercise, VO2 averaged 14.5+/-3.6 mL. kg-1. min-1; LVAD flow, 8.0+/-1.3 L/min; Fick cardiac output, 11.4+/-3.3 L/min; and pulmonary capillary wedge pressure, 13+/-4 mm Hg. Seven patients remained normotensive and could exercise at a fixed rate of 20 cycles/min. In these patients, peak VO2 declined from 17.3+/-3.9 to 13.0+/-6.1 mL. kg-1. min-1. In one of these patients, the device was explanted. CONCLUSIONS: Significant myocardial recovery after LVAD therapy in patients with end-stage congestive heart failure occurs in a small percentage of patients. Most of these patients have dilated cardiomyopathy. Exercise testing may be a useful modality to identify those patients in whom the device can be explanted.

Adolescent↗
PubMed1998

Comparison of exercise performance in patients with chronic severe heart failure versus left ventricular assist devices.

BACKGROUND: Left ventricular assist devices (LVADs) are frequently used as a bridge to cardiac transplantation and may be useful as long-term therapy. The purpose of this study was to compare the exercise performance of LVAD patients with that of ambulatory heart failure patients. METHODS AND RESULTS: Exercise testing with hemodynamic and respiratory gas measurements was performed in 65 congestive heart failure (CHF) patients (age 53+/-10 years) and 20 LVAD patients (age 49+/-8 years). Peak Vo2 was significantly higher in the LVAD than the CHF patients (CHF, 12+/-3; LVAD, 15. 9+/-3.8 mL . kg-1 . min-1; P<0.001), as was the Vo2 at the anaerobic threshold (CHF, 8.1+/-2.1; LVAD, 12.2+/-2.9 mL . kg-1 . min-1; P<0.001). At rest, mean arterial blood pressure (CHF, 87+/-11; LVAD, 94+/-9 mm Hg) and cardiac output (CHF, 4+/-1; LVAD, 4. 9+/-0.9 L/min) were increased, whereas mean pulmonary artery pressure (CHF, 28+/-11; LVAD, 18+/-4 mm Hg) and pulmonary artery wedge pressure (CHF, 16+/-10; LVAD 5+/-3 mm Hg) were reduced (all P<0.01). At peak exercise, heart rate (CHF,125+/-24; LVAD, 148+/-24 bpm), blood pressure (CHF, 87+/-14; LVAD,96+/-12 mm Hg), and cardiac output (CHF, 7.6+/-2.2; LVAD, 11.2+/-2.6 L/min) were higher (all P<0. 01), whereas mean pulmonary artery pressure (CHF, 48+/-12; LVAD, 30+/-5 mm Hg) and mean pulmonary capillary wedge pressure (CHF, 31+/-11; LVAD, 14+/-6 mm Hg) were lower in the LVAD group (both P<0. 001). In the LVAD patients, Fick cardiac output was higher than LVAD flow sensor value measurements (Fick, 11.6+/-2.5; LVAD, 8.1+/-1.2 L/min; P<0.001). CONCLUSIONS: Hemodynamic measurements at rest and during exercise are significantly improved in patients with devices compared with those in ambulatory heart failure patients awaiting cardiac transplantation. Similarly, the exercise capacity of device patients is better than that of transplant candidates and in the majority of patients is similar to that of patients with mild CHF.

Adult↗
PubMed1998

High-resolution restriction maps of bacterial artificial chromosomes constructed by optical mapping.

Large insert clone libraries have been the primary resource used for the physical mapping of the human genome. Research directions in the genome community now are shifting direction from purely mapping to large-scale sequencing, which in turn, require new standards to be met by physical maps and large insert libraries. Bacterial artificial chromosome libraries offer enormous potential as the chosen substrate for both mapping and sequencing studies. Physical mapping, however, has come under some scrutiny as being "redundant" in the age of large-scale automated sequencing. We report the development and applications of nonelectrophoretic, optical approaches for high-resolution mapping of bacterial artificial chromosome that offer the potential to complement and thereby advance large-scale sequencing projects.

Chromosome Mapping↗
PubMed1998

Gender and savings in rural India.

"In this study we use data from rural India to examine the impact of the birth of a boy relative to the birth of a girl (i.e., the ¿gender shock') on the savings, consumption and income of rural Indian households. We find that the gender shock reduces savings for medium and large farm households, although there is no evidence that the shock affects savings for the landless and the small farm households. We also estimate the effect of the shock on income and consumption for the former group in order to determine the source of the drop in savings."

Asia↗
PubMed1997

Treatment of hairy-cell leukemia with cladribine: response, toxicity, and long-term follow-up.

PURPOSE: To analyze initial and long-term outcomes after treatment of patients with active hairy-cell leukemia (HCL) with a single cycle of cladribine (2-CdA). PATIENTS AND METHODS: Forty-nine patients with active HCL were treated with 2-CdA by continuous intravenous infusion at 0.1 mg/kg/d for a total of 7 days at the Long Island Jewish Medical Center between September 1990 and August 1992. Here we report on all patients followed-up until April 1996. RESULTS: At 3 months after treatment, complete response (CR) occurred in 37 patients (76%) and partial response (PR) occurred in 12 patients (24%), for an overall response rate of 100% (95% confidence interval, 94% to 100%). At a median follow-up of 55 months, the relapse-free survival is 80% and overall survival is 95%. Ten patients (20%) have relapsed. Of the 26 patients in whom lymphocyte phenotyping was performed, four were found to have a CD25-negative phenotype. All four of these patients had PRs only and all relapsed. Eight patients have been re-treated with 2-CdA, and all achieved at least a partial remission; two of these have already relapsed with remission durations of less than 1 year. Five second malignancies have occurred in four patients. CONCLUSION: With a median follow-up of more than 4 years, 39 patients (80%) continue in remission. Only two deaths have occurred. A CD25-negative phenotype may predict for a poorer response to 2-CdA. Patients who relapse may be re-treated with 2-CdA, but subsequent remissions may be of shorter duration. There has not been a markedly increased incidence of second malignancies or late opportunistic infections.

Adult↗
PubMed1996

Relapse of hairy cell leukemia after 2-chlorodeoxyadenosine: long-term follow-up of the Northwestern University experience.

Although 2-chlorodeoxyadenosine (2-CdA) is effective in inducing complete remissions (CRs) in the majority of patients with hairy cell leukemia (HCL), neither the actual relapse rate, the clinical factors that may predict relapse, the long-term outcome, nor the response rate to re-treatment at relapse has been clearly determined. Fifty-two consecutive patients with previously untreated or treated HCL were treated with 2-CdA at a dose of 0.1 mg/kg/d by continuous intravenous infusion for 7 days. Of 50 assessable patients, 40 (80%) achieved CR, and 9 (18%) achieved partial remission (PR). A total of 7 patients (14%) have relapsed, at a median duration of 24 months (range, 12 to 44). Of the 7 relapsed patients, 5 were re-treated with a second cycle of 2-CdA; 2 achieved a second CR and 3 attained a PR. The progression-free survival (PFS) rate is 72% at 4 years for all 52 patients and 83% for patients achieving CR. The overall survival (OS) rate is 86% at 4 years. Only prior therapy was predictive of relapse. The majority of patients achieve durable CRs with a single cycle of 2-CdA. The relapse rate is low and the long-term prognosis is excellent. The few patients who relapse can attain second remissions after re-treatment with 2-CdA.

Adult↗
PubMed1996

Interaction between the phosphotyrosine binding domain of Shc and the insulin receptor is required for Shc phosphorylation by insulin in vivo.

Stimulation of the insulin receptor (IR) results in tyrosine phosphorylation of the intermediate molecules insulin receptor substrate-1 (IRS-1), IRS-2, and Shc, which then couple the IR to downstream signaling pathways by serving as binding sites for signaling molecules with SH2 domains. It has been proposed that direct binding of IRS-1, IRS-2, and Shc to an NPX-Tyr(P) motif in the juxtamembrane region of the IR is required for tyrosine phosphorylation of these molecules by the IR. In this regard, Shc and IRS-1 contain domains that are distinct from SH2 domains, referred to as the phosphotyrosine binding (PTB) or phosphotyrosine interaction (PI) domains, which bind phosphotyrosine in the context of an NPX-Tyr(P) motif. To further clarify the role of the Shc PTB/PI domain, we identified a mutation in this domain that abrogated binding of Shc to the IR in vitro. Interestingly, this mutation completely abolished Shc phosphorylation by the IR in vivo whereas mutation of the arginine in the FLVRES motif of the Shc SH2 domain did not affect Shc phosphorylation by insulin. In addition, we identified specific amino acids on the IR that are required for the IR to stimulate Shc but not IRS-1 phosphorylation in vivo. As with the PTB/PI domain Shc mutant, the ability of these mutant receptors to phosphorylate Shc correlates with the binding of the PTB/PI domain of Shc to similar sequences in vitro. These findings support a model in which binding of the PTB/PI domain of Shc directly to the NPX-Tyr(P) motif on the IR mediates Shc phosphorylation by insulin.

3T3 Cells↗
PubMed1996

Activation of coagulation and fibrinolytic pathways in patients with left ventricular assist devices.

Left ventricular assist devices have provided successful supportive therapy for patients awaiting cardiac transplantation for extended periods of time. Although thromboembolic events have complicated support with these devices, the HeartMate left ventricular assist device developed by Thermo Cardiosystems, Inc., Woburn, Massachusetts, was specifically designed with a textured blood-contacting surface to minimize this risk. Clinical experience with this device has been encouraging, inasmuch as minimal thromboembolic complications have occurred despite the absence of anticoagulation. The coagulation and fibrinolytic pathways in these individuals were investigated to better understand the hematologic status of patients treated with the Thermo Cardiosystems device. Despite apparently normal prothrombin and activated partial thromboplastin times, as well as platelet counts, evidence of significant thrombin generation and fibrinolysis was present. To eliminate underlying cardiac failure as the responsible factor for these abnormalities, we made similar measurements in patients with end-stage heart failure who were not supported by an assist device or anticoagulation. These measurements revealed no evidence of thrombin generation or fibrinolysis. These data demonstrate that patients supported with a left ventricular assist device, while successfully sustained without systemic anticoagulation, nevertheless have evidence of activation of coagulation. These phenomena appear to be related to the presence of the device rather than to the underlying cardiac abnormalities. Although procoagulant and fibrinolytic pathways are apparently balanced in these patients, these data underscore the potential for the development of bleeding or thrombosis in clinically relevant settings.

Adolescent↗
PubMed1996

Pharmacokinetic study of oral and bolus intravenous 2-chlorodeoxyadenosine in patients with malignancy.

PURPOSE: This study was designed to evaluate the absolute bioavailability (F value) of 2-chlorodeoxyadenosine (cladribine; 2-CdA) after multiple oral administrations, and the intersubject variability after oral and 2-hour intravenous (IV) administration schedules in patients with malignancy. PATIENTS AND METHODS: Patients with advanced malignancies were eligible. There were two treatment cycles; during cycle 1, patients received 2-CdA solution at 0.28 mg/kg/d orally under fasting conditions for 5 consecutive days concomitantly with omeprazole, and 4 weeks later during cycle 2 patients received 2-CdA as a 2-hour IV infusion of 0.14 mg/kg/d for 5 consecutive days. Serial blood samples for 2-CdA plasma levels were obtained after drug administrations on days 1 and 5 during each treatment cycle. RESULTS: Ten patients completed cycles 1 and 2. The F value of oral 2-CdA measured on days 1 and 5 was 37.2% and 36.7%, respectively. For both oral and IV multiple administrations, there was no significant accumulation in maximum concentration (Cmax), and the intersubject variabilities (coefficient of variation [CV], approximately 40%) in Cmax and area under the concentration-time curve from 0 to 24 hours [AUC(0-24)] values were comparable for both routes on days 1 and 5. A three-compartment open model was applied to the plasma concentration data after oral and IV administrations and resulted in good agreement between observed and simulated concentration-time profiles. Neutropenia was the principal adverse event observed when 2-CdA was administered orally and IV. CONCLUSION: The F value of 2-CdA after oral administration was approximately 37% and there were no cumulative differences in bioavailability observed on multiple dosing of the drug. The absorption and disposition characteristics of oral 2-CdA were linear and predictable with this dosing regimen.

Administration, Oral↗
PubMed1996

Failure to Diagnose Failure to Grow.

A 14-year-old female presented with a 3-week history of sore throat, hoarseness, croupy nonproductive cough, fever, diarrhea, and 5.5-kg weight loss. She was a poor student and "picky eater," and both her current weight and height (18.5 kg and 128 cm) were far below the fifth percentile. Her apparent failure to thrive was a source of concern, and although her diarrhea appeared to be acute, she began to have guaiac-positive stools, and admitted to chronic episodes of diarrhea and recurrent abdominal pains. A colonoscopy revealed chronic aphthous ulcers consistent with Crohn's disease of the large bowel. She was discharged on nutritional supplements, high-dose prednisone therapy, and mesalimine delayed-release tablets.

Journal Article↗